Sustained cortical and subcortical neuromodulation induced by electrical tongue stimulation

Abstract

This pilot study aimed to show that information-free stimulation of the tongue can improve behavioral measures and induce sustained neuromodulation of the balance-processing network in individuals with balance dysfunction. Twelve balance-impaired subjects received one week of cranial nerve non-invasive neuromodulation (CN-NINM). Before and after the week of stimulation, postural sway and fMRI activation were measured to monitor susceptibility to optic flow. Nine normal controls also underwent the postural sway and fMRI tests but did not receive CN-NINM. Results showed that before CN-NINM balance-impaired subjects swayed more than normal controls as expected (p ≤ 0.05), and that overall sway and susceptibility to optic flow decreased after CN-NINM (p ≤ 0.005 & p ≤ 0.05). fMRI showed upregulation of visual sensitivity to optic flow in balance-impaired subjects that decreased after CN-NINM. A region of interest analysis indicated that CN-NINM may induce neuromodulation by increasing activity within the dorsal pons (p ≤ 0.01).

Fig. 1

Brainstem anatomy and ROI location. a Axial diagram of the brainstem at the pontomedullary junction shows the proximity of the Vestibular nuclei complex (VC) to the Trigeminal (T) and Solitary (S) nuclei, the apparent brainstem targets of CN-NINM. b A region of interest (ROI) was drawn on a high-resolution atlas of the brainstem and cerebellum (right) to analyze the BOLD signal changes in the area of overlap between the vestibular, trigeminal, and solitary nuclei bilaterally. IO Inferior Olive; ICP Inferior Cerebellar Peduncle; L/R Left/Right; I/S Inferior/Superior; V/D Ventral/Dorsal)

Fig. 2

Tongue stimulation device and CN-NINM waveform. a The 12×12 electrode array, here shown next to a quarter for reference, is placed on the anterior surface of the tongue and is held in place by pressure of the tongue to the roof of the mouth. b CN-NINM stimulation consists of three square-wave pulse bursts with a 200 Hz intraburst and 50 Hz interburst frequency. The stimulation voltage is adjusted at the start of every stimulation session and has a maximum of 24 V

Fig. 3

Average difference of the power of head sway velocity (P_vel) measurements in response to the visual stimuli. The ANOVA showed a decreased sway in response to optic flow in the post-CN-NINM group compared to the pre-CN-NINM group. Two-sample t-tests show increased sway in the pre-CN-NINM group compared to the normal controls but no difference between the post-CN-NINM group and the controls. Error bars are the standard error of the mean. * - p<0.05

Fig. 4

The BOLD percent signal change of the CBrot–CBstat contrast for each subject averaged over the brainstem ROI. The ANOVA revealed increased activation in the post-CN-NINM group compared to the pre-CN-NINM group. Normal controls showed greater activation compared to the pre-CN-NINM group but not the post-CN-NINM group. Error bars are 95% confidence intervals about the mean. * - p<0.005, ** - p<0.01

Fig. 5

Activation patterns of the CBrot–CBstat contrast from the one-sample t-tests (Pre: pre-CN-NINM, Post: post-CN-NINM, Norm: normal controls) and the two-sample t-test comparing the pre-CN-NINM group to normal controls (Pre-N). All images are thresholded at α≤0.001 (|T₁₁|≥4.0 for Pre and Post, |T₈| ≥ 4.5 for Norm, and |T₂₀|≥3.5 for Pre-N). Only clusters with a volume greater than 496 µl (128 µl for subcortical structures) are displayed. All Z values are in MNI coordinates

Fig. 6

Activation patterns from the ANOVA analysis comparing the pre-CN-NINM group to the post-CN-NINM group. Images are thresholded at α≤0.001 (|T₄₄|≥3.2). Only clusters with a volume greater than 496 µl (128 µl for subcortical structures) are displayed. All Z values are in MNI coordinates